Research Summary

Vutrisiran Slows Left Atrial Strain Worsening in ATTR-CM: Secondary HELIOS-B Analysis

Edited by:
Brian McCurdy

Key Highlights

  • Left atrial strain was substantially below normal among 644 patients with measurable strain in HELIOS-B.
  • Worse reservoir and contractile strain independently predicted mortality and recurrent cardiovascular events.
  • Left atrial volume index was not associated with the evaluated clinical outcomes.
  • Baseline strain did not significantly modify vutrisiran’s effect on mortality and recurrent cardiovascular events.

Vutrisiran attenuated worsening left atrial function at 30 months compared with placebo in a secondary analysis of the HELIOS-B randomized clinical trial published in JAMA Cardiology. Left atrial dysfunction was common among patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM) and independently associated with adverse outcomes.

The post hoc analysis evaluated left atrial structure and function in the phase 3 trial, which enrolled 655 patients at 87 sites in 26 countries between December 2019 and August 2021. Participants received vutrisiran, 25 mg subcutaneously every 3 months, or placebo. Median follow-up was 36 months.

Investigators assessed left atrial volume index and reservoir, conduit, and contractile strain. They examined associations with all-cause mortality and recurrent cardiovascular events, recurrent heart failure hospitalizations, and incident atrial fibrillation, along with treatment effects on left atrial measures at 30 months.

Study Findings

Among 644 patients with measurable left atrial strain, median age was 77 years, 7.5% were female, and 88.4% had wild-type ATTR. Mean reservoir, conduit, and contractile strain were 9.5%, 6.9%, and 4.2%, respectively—substantially below normal. Worse reservoir strain accompanied more advanced disease, atrial fibrillation, and left ventricular dysfunction. For each reported 5% worsening, reservoir strain was independently associated with mortality and recurrent cardiovascular events (hazard ratio [HR], 1.37; 95% CI, 1.13–1.68; P = .002), as was contractile strain (HR, 1.53; 95% CI, 1.08–2.17; P = .02). Both measures also independently predicted recurrent heart failure hospitalization and incident atrial fibrillation; left atrial volume index did not predict these outcomes.

At 30 months, between-group differences favored vutrisiran by 1.2 percentage points for reservoir strain (95% CI, 0.4–1.9), 0.8 points for conduit strain (95% CI, 0.3–1.4), and 0.8 points for contractile strain (95% CI, 0–1.6). Baseline strain did not significantly modify the treatment effect on mortality and recurrent cardiovascular events, with interaction P values of .60, .58, and .47, respectively.

Clinical Implications

According to the authors, left atrial dysfunction indicates a worse prognosis in ATTR-CM. They interpreted the treatment findings as supporting the importance of left atrial function in disease pathophysiology and vutrisiran’s ability to attenuate worsening atrial myopathy.

Expert Commentary

“LA dysfunction is common among patients with ATTR-CM and portends a worse prognosis,” the researchers concluded.

Reference

Jering KS, Manafi A, Claggett BL, et al. Left atrial structure and function, clinical outcomes, and efficacy of vutrisiran in transthyretin amyloidosis with cardiomyopathy: a secondary analysis of the HELIOS-B randomized clinical trial. JAMA Cardiol. 2026;11(10):971-980. doi:10.1001/jamacardio.2026.2992